Signara Gueye

The global CTX-M pandemic is considered a plasmid-driven phenomenon, yet chromosomal integration of bla _CTX-M has been reported in various settings. Screening 451,174 publicly available E. coli genomes and retaining 2,269 CTX-M- E. coli long-read or hybrid assemblies, we found that 33.5% carried at least one chromosomally integrated bla _CTX-M . Chromosomal integration was strongly structured by E. coli lineage and CTX-M variant, reaching 68.5% in ST38 and 43.9% in ST131. In the latter, integration rates varied between subclades with modelling, suggesting recent acceleration within the ST131-C2 subclade. Additional resistance genes were frequently co-integrated with bla _CTX-M (33%), with architectures largely inherited from plasmid-borne structures. Integrations were mainly IS Ecp1 - or IS 26 -mediated (77.3% and 18.9%, respectively) and occurred across the entire E. coli chromosome without spared zones. bla _CTX-M chromosomal integration is a widespread, lineage-structured component of the CTX-M pandemic, providing stable vertical inheritance that complements or may supplant plasmid-mediated dissemination in successful ESBL- E. coli clones.

Carbapenem-resistant Acinetobacter baumannii (CRAB) are rare in France and are usually reported in intensive care units (ICU). In 2021/2022, an unexpected increase in the incidence of CRAB isolates co-producing OXA-23 and NDM carbapenemases (OXA-23/NDM-CRAB) in several hospitals in the north of Paris prompted a common retrospective investigation. These strains were extremely resistant to both first- and second-line antibiotics, resulting in difficult-to-treat infections. We collected all cases of OXA-23/NDM-CRABs infection/colonisation between January 2020 and December 2022 in five northern Paris hospitals. Demographic and clinical data were collected for each patient. Isolates were sequenced using Illumina and representative isolates were sequenced using Nanopore. An OXA-23/NDM-CRAB was detected in 42 patients (mean age 61 years, M/F: 1.3), 58% of whom were hospitalised in a medical ward and 42% in an ICU, within three hospitals. Of these patients, 26% (11/42) were infected with CRAB, while 74% (31/42) were colonised. Two clonal strains spread over one year: ST ^Ox 231 ^/Pas 1 in hospital 1 (n = 12) and hospital 3 (n = 13) differing by 0–16 SNPs and ST ^Ox 1632 ^/Pas 600 in hospital 2 (n = 13) differing by 0–17 SNPs. WGS and epidemiological investigation identified the likely index patient for hospitals 1 and 3 outbreaks as a patient repatriated from hospitalisation in Cape Verde. This patient was not screened for multidrug resistant bacteria carriage during hospitalisation in hospital 1 and was detected positive 5 days after admission to the ICU in hospital 3. All outbreaks were stopped after infection control teams’ intervention. This is the first description of OXA-23/NDM-CRAB outbreaks in metropolitan France. The simultaneous dissemination of two clonal OXA-23/NDM-CRAB strains in Parisian hospitals is unusual, particularly in non-ICU settings. Medical and nursing staffs must be sensitized to the importance of screening patients returning from abroad, including for CRAB, to prevent future outbreaks.

Importance: Infective endocarditis (IE) caused by Staphylococcus aureus is associated with high mortality, approximately 20% to 30%, mostly in the first month, with no improvement in recent decades. Current opinion is that antistaphylococcal penicillin and cefazolin are equally effective in treating methicillin-susceptible S aureus (MSSA) IE, and both are recommended as possible first-line treatments. Most MSSA strains carry the β-lactamase blaZ gene, and some blaZ-positive strains exhibit an inoculum effect, meaning increased minimum inhibitory concentrations at high inoculum. This reduced susceptibility to an antibiotic at high bacterial inoculum may be particularly relevant in IE, where vegetations have very high bacterial densities.Objective: To evaluate the association between phenotypic characteristics of S aureus isolates, β-lactam used, and outcome in patients with MSSA IE.Design, Settings, and Participants: This retrospective case series included MSSA cases treated at 3 French university hospitals between February 2016 and February 2022. The study included patients who had clinical isolates available and had definite or possible S aureus IE that involved native or prosthetic valves. Data were analyzed from July 2023 to June 2024.Main Outcomes and Measures: MSSA isolates were tested for the presence of blaZ and for inoculum effects to cefazolin and oxacillin. The association between first-month mortality and the β-lactam used, the presence of blaZ, and the presence of an inoculum effect to the treatment received was evaluated.Results: This study included 216 patients with MSSA IE (median [IQR] age, 65 [49-73] years; 152 [70.4%] male) who were treated with antistaphylococcal penicillin (139 [64.4%]) or cefazolin (77 [35.6%]). One-month mortality of left-sided IE was 44 of 180 patients (24.4%), with no overall difference between patients treated with antistaphylococcal penicillin or cefazolin. However, 1-month mortality was higher in patients infected with blaZ-positive strains than with blaZ-negative strains (38 of 129 [29.5%] vs 6 of 51 [11.8%]; P = .01), and with strains with an inoculum effect to the β-lactam received than with strains without an inoculum effect (25 of 62 [40.3%] vs 13 of 67 [19.4%]; P = .005). On multivariable analysis, the presence of an inoculum effect was independently associated with first-month mortality (HR, 2.84; 95% CI, 1.28-6.30; P = .01).Conclusions and Relevance: In this case series of MSSA IE, the presence of an inoculum effect to the β-lactam received was a risk factor for death in the first month. Phenotyping MSSA isolates for inoculum effect may guide β-lactam choice and improve outcomes.